title: Neuropathological review of 138 cases genetically tested for X-linked hydrocephalus: evidence for closely related clinical entities of unknown molecular bases.
abstract: L1 syndrome results from mutations in the L1CAM gene located at Xq28. It encompasses a wide spectrum of diseases, X-linked hydrocephalus being the most severe phenotype detected in utero, and whose pathophysiology is incompletely understood. The aim of this study was to report detailed neuropathological data from patients with mutations, to delineate the neuropathological criteria required for L1CAM gene screening in foetuses by characterizing the sensitivity, specificity and positive predictive value of the cardinal signs, and to discuss the main differential diagnoses in non-mutated foetuses in order to delineate closely related conditions without L1CAM mutations. Neuropathological data from 138 cases referred to our genetic laboratory for screening of the L1CAM gene were retrospectively reviewed. Fifty-seven cases had deleterious L1CAM mutations. Of these, 100 % had hydrocephalus, 88 % adducted thumbs, 98 % pyramidal tract agenesis/hypoplasia, 90 % stenosis of the aqueduct of Sylvius and 68 % agenesis/hypoplasia of the corpus callosum. Two foetuses had L1CAM mutations of unknown significance. Seventy-nine cases had no L1CAM mutations; these were subdivided into four groups: (1) hydrocephalus sometimes associated with corpus callosum agenesis (44 %); (2) atresia/forking of the aqueduct of Sylvius/rhombencephalosynapsis spectrum (27 %); (3) syndromic hydrocephalus (9 %), and (4) phenocopies with no mutations in the L1CAM gene (20 %) and in whom family history strongly suggested an autosomal recessive mode of transmission. These data underline the existence of closely related clinical entities whose molecular bases are currently unknown. The identification of the causative genes would greatly improve our knowledge of the defective pathways involved in these cerebral malformations.
authors.affiliation: Department of Pathology, Lariboisière Hospital, APHP, 2 Rue Ambroise Paré, 75010, Paris, France. homa.adle@inserm.fr
authors.forename: Homa
authors.initials: H
authors.lastname: Adle-Biassette
authors.forename: Pascale
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authors.lastname: Saugier-Veber
authors.forename: Catherine
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authors.lastname: Fallet-Bianco
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Férecheté
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authors.lastname: Razavi
authors.forename: Nathalie
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authors.lastname: Drouot
authors.forename: Anne
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authors.lastname: Bazin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Beaufrère
authors.forename: Bettina
authors.initials: B
authors.lastname: Bessières
authors.forename: Sophie
authors.initials: S
authors.lastname: Blesson
authors.forename: Martine
authors.initials: M
authors.lastname: Bucourt
authors.forename: Dominique
authors.initials: D
authors.lastname: Carles
authors.forename: Louise
authors.initials: L
authors.lastname: Devisme
authors.forename: Frédérique
authors.initials: F
authors.lastname: Dijoud
authors.forename: Blandine
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authors.lastname: Fabre
authors.forename: Carla
authors.initials: C
authors.lastname: Fernandez
authors.forename: Dominique
authors.initials: D
authors.lastname: Gaillard
authors.forename: Marie
authors.initials: M
authors.lastname: Gonzales
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jossic
authors.forename: Madeleine
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authors.lastname: Joubert
authors.forename: Nicole
authors.initials: N
authors.lastname: Laurent
authors.forename: Brigitte
authors.initials: B
authors.lastname: Leroy
authors.forename: Laurence
authors.initials: L
authors.lastname: Loeuillet
authors.forename: Philippe
authors.initials: P
authors.lastname: Loget
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.forename: Jelena
authors.initials: J
authors.lastname: Martinovic
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Perez
authors.forename: Daniel
authors.initials: D
authors.lastname: Satge
authors.forename: Martine
authors.initials: M
authors.lastname: Sinico
authors.forename: Mario
authors.initials: M
authors.lastname: Tosi
authors.forename: Jacques
authors.initials: J
authors.lastname: Benichou
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D002535:Cerebral Aqueduct / Q000002:abnormalities* / Q000473:pathology*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000473:pathology*; D006801:Humans; D006849:Hydrocephalus / Q000473:pathology*; D007231:Infant, Newborn; D009154:Mutation / Q000235:genetics; D009422:Nervous System Diseases / Q000235:genetics / Q000473:pathology*; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy
chemical_list: D039842:Neural Cell Adhesion Molecule L1